Lubricant soluble fluorescent agent and method for its use in a system for detection of lubricant coatings

ABSTRACT

A method for visualization of a lubricant coating on a surface of an article includes dissolving a fluorescent agent into a lubricant. The method then includes applying the fluorescenated lubricant to coat a surface of the article. The coated article is then irradiated with an electromagnetic radiation capable of inducing a fluorescent emission in the fluorescent agent and the fluorescent emission is observed to detect the coverage of the lubricant on the surface of the article.

This is a division of application Ser. No. 08/606,718, filed Feb. 27,1996, now U.S. Pat. No. 5,667,840.

FIELD OF INVENTION

The present invention generally relates to the coating of objects andmore particularly to materials, a method and a system useful forvisualization of a lubricant coating on the surface of medical devices.

BACKGROUND OF THE INVENTION

Medical devices are often assembled from components formed from manydifferent materials. It often is necessary to apply a coating of alubricant to one or more of the components so that a component of onematerial will readily slide against a component of another material.Examples of this type of application are catheters with guidewires,over-the-needle catheters, syringe plunger stoppers within syringebarrels, needles for penetration of blood collection tube stoppers andthe like. In other medical device applications, a lubricant is appliedto a device to ease its penetration into the body. Examples of theseapplications are surgical blades, hypodermic needles, peripheral venouscatheters and the like.

In all of these medical device lubrication applications, there arestrict requirements on the amounts of lubricant, the uniformity of theapplication and a need to avoid contamination of the device with foreignmaterial other than the lubricant. A further requirement on applicationof lubricant results from the high volume production requirements oftenresulting in the use of high speed assembly equipment. Thus, anylubricant application must be precise and compatible with high volumeproduction.

Currently, a commonly used lubricant for medical devices is "silicone,"i.e., polydimethylsiloxane having a Brookfield viscosity between about1,000 and 1,000,000 centistokes (cs). For some applications, thesilicone is applied "neat," i.e., without solvent. An example of neatapplication of silicone to syringe plunger stoppers is disclosed in U.S.Pat. No. 5,207,293 to Eden et al. This patent discloses a method andapparatus for lubricating syringe stoppers by moving the stoppersbetween a pair of wheels that are positioned partially in a reservoircontaining lubricant so that, with rotation of the wheels, lubricant istransferred to the stoppers.

Another commonly used neat application method is tumbling a measuredquantity of small parts, such as stoppers, with a measured quantity oflubricant so that the parts acquire a coating of the lubricant.

Silicone lubricant also may be sprayed onto the parts either neat or ina carrier solvent. Neat spraying has been found to work well forinterior surfaces such as inside syringe barrels. Solvent based dippingor spraying is commonly used for coating hypodermic needles andpercutaneous catheters. Chlorofluorcarbon solvents have proven to bevery satisfactory for the delivery of silicone onto medical devicesbecause they are non-toxic, non-flammable, inert, evaporate rapidlywithout leaving residue and are available in very high purity.Unfortunately, because of the belief that chlorofluorocarbon solventsare responsible for destruction of ozone in the upper atmosphere, mostcommonly used chlorofluorocarbon solvents will no longer be available.Alternate solvents such as hydrocarbons are flammable, and aqueous basedsystems generally are not practical for silicones.

When silicone lubricant is applied to a device in a solvent, the deviceis generally sprayed with or dipped in a dilute solution of the siliconecontaining solvent. In these application techniques, the solution with alow concentration of lubricant is generally present in excess. Thedilute solution is often sprayed or flowed over the device being coated,in excess of the amount required to coat it. Thus, as long as thisexcess is maintained and monitored, there is substantial confidence thatthe medical devices have a substantially uniform coating of at least theminimum desired quantity. When the silicone is applied directly or"neat," there is not the same level of confidence that the desiredamount of silicone is being applied. The actual amount of siliconelubricant applied to each individual device, such as an intravenouscatheter or hypodermic needle is very small.

Two recent United States Patent Applications, commonly assigned with thepresent application, Ser. Nos. 08/509,393 and 08/509,395, disclose theneat application of polydimethylsiloxane to medical devices. An examplegiven the in these referenced disclosures is the application of 12,500cs. polydimethylsiloxane to 14 gauge intravenous catheters. In theexamples, the referenced applications disclose that about 0.3±0.075 mgis applied to each individual catheter. Polydimethylsiloxane is a clearwater white liquid. It is available in a wide range of viscositiesranging from about 50 cs. to about 1,000,000 cs. Because of the physicalcharacteristics of polydimethylsiloxane and the small amount applied toeach catheter, it is difficult to differentiate between a lubricatedcatheter and an unlubricated catheter by visual comparison. Thus, it isalmost impossible to determine visually and rapidly if an individualcatheter has the desired uniform coating. Since these catheters aremedical devices, they must be manufactured according to GoodManufacturing Practices (GMP) as defined by the Food and DrugAdministration. An important aspect of GMP is developing the ability tovalidate and to monitor production processes.

One way to determine the amount of silicone on a catheter is tocarefully weigh identified catheters, feed them through the process andthen reweigh them to determine the silicone loading. This techniqueallows a determination of the gross amount of polydimethylsiloxane on anindividual catheter, but it is considered a "destructive" test, i. e.,the identified catheter generally cannot be put back into the process.Additionally, with weighing, no determination can be made of theuniformity of the application. Another destructive method involveswashing the polydimethylsiloxane off the catheter with a solvent,evaporating the solvent and weighing the residual polydimethylsiloxane.Again, washing does not address the need to determine if the applicationis uniform.

Because of the GMP requirements that the production of medical devicesbe validated and controlled, there is a need for a non-destructivemethod to monitor the application of lubricants to their surfaces.Additionally, since many medical devices are single-use and produced inlarge volumes, if the monitoring method was relatively inexpensive andcompatible with high volume, high speed manufacturing processes, anadditional benefit to the art of medical device manufacture would berealized. Materials, a method and a system for visualization ofpolydimethylsiloxane on the surface of a medical device are disclosedbelow.

SUMMARY

A method of the present invention for visualization of apolydimethylsiloxane coating on a surface of a medical device includesdissolving a fluorescent agent into a polydimethylsiloxane lubricant andapplying the fluorescenated polydimethylsiloxane lubricant to thesurface of the medical device. The method includes irradiating thesurface with the lubricant with an electromagnetic radiation capable ofinducing a fluorescent emission in the fluorescent agent. The methodfurther includes detecting the fluorescent emission to thereby determinethe degree of coverage of the polydimethylsiloxane on the surface of themedical device.

The method of the invention allows non-destructive visualization ofsmall quantities applied in thin layers of polydimethylsiloxanelubricant for confirming its presence on the surface of small medicaldevices such as catheters, hypodermic needles and the like.Additionally, the method further allows non-destructive evaluation ofthe degree or uniformity of coverage of the surface of the device. Asystem that utilizes the method of the invention includes a source ofelectromagnetic radiation capable of inducing a fluorescent emission inpolydimethylsiloxane having a fluorescing agent and a detector fordetecting the emission. The system of the invention may be easilyincorporated into an assembly line and used for monitoring large numbersof medical devices at a rate comparable to the rate of assembly.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic perspective view of a system using the preferredmethod of the present invention;

FIG. 2 is an enlarged schematic illustration of the irradiation anddetection portions of the system of FIG. 1; and

FIG. 3 is a block diagram of the system of the present invention asincorporated into an assembly line.

DETAILED DESCRIPTION

While this invention is satisfied by embodiments in many differentforms, there are shown in the drawings and herein described in detail apreferred embodiment of the invention with the understanding that thepresent disclosure is to be considered exemplary of the principles ofthe invention and is not considered to limit the invention to theembodiment illustrated. The scope of the invention is measured by theappended claims and their equivalents.

Referring to FIGS. 1-3, a preferred inspection system 10 of the presentinvention for determining a preselected degree of coverage of apolydimethylsiloxane lubricant on a surface 12 of a medical device 14includes a source 16 of an electromagnetic radiation 18, preferablyUltraviolet (UV) radiation, for irradiation of a surface 12 of a medicaldevice 14, such as a catheter 20 having thereon a coating 22 ofpolydimethylsiloxane. The use of the catheter as an example of medicaldevice 14 is only intended to be illustrative of the principles of theinvention and is not limitive of the invention to catheters. Applicationof the system to other medical devices, other objects or articles with alubricant coating such as polydimethylsiloxane and the like isconsidered to be within the scope of the invention.

Polydimethylsiloxane coating 22 includes a fluorescent agent dissolvedtherein that provides a fluorescent emission 24 when the coating isirradiated by electromagnetic radiation 18. For the purpose of thisdescription the polydimethyl siloxane or other lubricant with thefluorescent agent dissolved therein is said to be "fluorescenated".

System 10 may be used by an inspector to visually discriminate betweendevice 14 having sufficient coating 22 to fulfill the manufacturer'sspecification and those that do not. The visual discrimination isschematically illustrated in FIG. 2, where fluorescent emission 24allows visual differentiation between one catheter surface 26 with auniform coating 22 and another catheter having only a partial coating 22leaving a surface 28 that has no, or an uneven, coating.

System 10 preferably includes a detector 30 positioned to detect andrespond to fluorescent emission 24 from the fluorescent agent in coating22. Preferably, detector 30 has a maximum sensitivity to electromagneticradiation having a wavelength between about 450 nm to about 520 nm. As aresponse, detector 30 generates a signal that preferably has a valueproportional to the degree (coated area 26/uncoated area 28) of coverageof surface 12 by polydimethylsiloxane coating 22. Detector 30 preferablyincludes a capability to be adjusted to a preselected minimum thresholdsensitivity value substantially corresponding to a preselected minimumdegree of coverage of surface 12. Detector 30 preferably generates anoutput signal of the results of this comparison. Alternatively, detector30 may include the capability to be adjusted to both a preselectedminimum and maximum sensitivity values substantially corresponding to apreselected minimum and maximum degree of coverage of surface. In thisalternative case, detector 30 preferably generates an output signal ofthe results of this comparison.

System 10 is useful in an assembly process line 40, as schematicallyillustrated in FIG. 1 and in the block diagram of FIG. 3. In thispreferred application, the output signal from detector 30 may bedisplayed on a display 32, or more preferably, as is schematically shownin the block diagram, the detector output signal may be coupled to adiverter/sorter 34 to divert devices having other than the preselecteddegree of,coating from a sample transport pathway 36 to a reject station38. Alternatively, the detector output may be connected to an alarm,line shut-down or the like.

In order to be effective in this application, the fluorescent agent musthave a degree of solubility in polydimethylsiloxane.Polydimethylsiloxane is an extremely hydrophobic material, and mostfluorescent dyes are virtually insoluble it. As is reported above and inthe cited references as an example, an individual medical device, suchas the intravenous catheter, has only about 0.3 mg ofpolydimethylsiloxane of 12,500 cs. lubricant applied to it. Thus, giventhe size and surface area of the part, the coating ofpolydimethylsiloxane on the device surface is less than about 1×10⁻³ mmthick. This fact, coupled with the physical properties of thepolydimethylsiloxane, renders addition of even an intensely colored dyeto the polydimethylsiloxane for visualization of the coating of littleutility. Additionally, since a catheter is a medical device, addition ofa substantial amount of a strongly colored dye is undesirable andsubjects the device to additional approval steps. Further, most commondyes are only dispersible, not soluble, in polydimethylsiloxane. A trialwhere about 0.3 percent (wt./wt.) of an intensely colored violet dye,Calco oil violet ZIRS, available from BASF Corp., was only dispersed,not dissolved, in polydimethylsiloxane, did not allow an observer toeasily determine if a uniform coating of polydimethylsiloxane waspresent on the catheter.

Preferred dyes for use in the system of the present invention include,but are not limited to,7-diethylamino-4-trifluoromethyl-2H-1-benzopyran-2-one, commonly knownas coumarin 481,7-dimethylamino-4-trifluoromethyl-2H-1-benzopyran-2-one, commonly knownas coumarin 485, mixtures thereof and the like. These dyes are made byExiton, Dayton, Ohio and available from Eastman Chemical, Kingsport,Tenn. The preferred dyes are soluble in 12,500 cs. polydimethylsiloxane.The preferred dyes fluoresce strongly about 510 nm (yellow-green) whenexcited with the preferred UV radiation. A sufficiently strongfluorescent emission to allow visual discrimination between coated anduncoated surface is present when the preferred dyes are dissolved inpolydimethylsiloxane at preferred concentrations between about 0.001parts to about 0.01 parts in about 1,000 parts polydimethylsiloxane.Given the approximate 0.3 mg application of polydimethylsiloxane percatheter, the preferred concentration range results in an actual amountof the dye on an individual catheter between about 0.2 to about 1×10⁻⁶g. Both of the preferred dyes have been subjected to a battery oftoxicity and mutagenicity tests at concentrations based on the actualdelivery amount and at higher concentrations. The results of thetoxicity and mutagenicity testing show no evidence of toxicity ormutagenicity for the preferred dyes. Other polydimethylsiloxane solublefluorescent dyes that are demonstrated to be non-toxic and non-mutagenicwould also be suitable and are within the scope of the presentinvention.

The fluorescent emission is sufficient to allow a visualdifferentiation, illustrated schematically in FIG. 2, between onecatheter with a uniform coated area 26 and the other catheter with bothcoated area 26 and uncoated area 28. FIG. 2 also schematicallyillustrates two detectors 30, one showing an acceptable result for thecatheter with uniform coating 26 and the other showing an unacceptableresult for the catheter with uncoated area 28 greater than a preselectedacceptable minimum value.

Preferably, electromagnetic radiation 18 from source 16 used toirradiate the surface of the devices coated with fluorescenatedpolydimethylsiloxane has a wavelength between about 300 nm to about 400nm. A high pressure mercury vapor lamp has an emission spectrum with awavelength maximum about 365 nm and is a preferred source of suitable UVradiation. Other sources having emission wavelength profiles differentthan the preferred high pressure mercury lamp would be suitable if theiremission is passed through a monochrometer or the like to adjust theiremission wavelength profile to generally approximate the emissionprofile of the preferred lamp. A suitable detector is a photometerhaving an adjustable threshold value and an adjustable sensitivity tofluorescent emission 24 having a wavelength between about 450 nm toabout 520 nm. An L4T-1-4 Luminescence Scanner made by SICK OpticElectronics, Inc., (Germany) has been found to be suitable. Otherphotometric detectors having generally similar wavelength responses andadjustment features would also be suitable.

The method and system of the invention are substantially compatible withcommon line assembly speeds and space requirements. Use of the methodand system of the invention provides a manufacturer of lubricateddevices with a simple and efficient way to fulfill GMP requirements.

What is claimed is:
 1. An inspection system for determining apreselected degree of coverage of a polydimethylsiloxane lubricant on asurface of a medical device comprising:a source of electromagneticradiation for irradiation of a surface of a medical device havingthereon a coating of polydimethylsiloxane, said polydimethylsiloxaneincluding a fluorescent agent at a concentration of between about 10⁻⁵ %to about 10⁻⁶ % dissolved therein, said irradiation being sufficient toinduce a fluorescent emission from said fluorescent agent; a detectorhaving a maximum sensitivity to electromagnetic radiation having awavelength between about 450 nm to about 520 nm, said detector beingpositioned to detect said fluorescent emission from said fluorescentagent in said polydimethylsiloxane and to generate a signal from saiddetector having a value proportional to the degree of coverage of thesurface with the polydimethylsiloxane; and means for receiving thesignal and comparing said value of the signal with a preselected valuecorresponding to a preselected degree of coverage of the surface of themedical device with the polydimethylsiloxane, said means furtherincluding a display to indicate the results of the comparison with thepreselected value thereby providing a determination of said preselecteddegree of coverage.
 2. The system of claim 1 wherein said fluorescentagent is selected from the group consisting of7-diethylamino-4-trifluoromethyl-2H-1-benzopyran-2-one,7-dimethylamino-4-trifluoromethyl-2H-1-benzopyran-2-one and mixturesthereof.
 3. The system of claim 1 further comprising transport means forpresenting a plurality of the medical devices to the radiation sourceand to the detector thereby enabling said system to monitor a pluralityof the medical devices.
 4. The system of claim 3 wherein said transportmeans further includes a sorting station responsive to said signal fromthe detector, said sorting station directing the medical devices havingother than said preselected degree of coverage to a reject station.